Many pharmaceuticals and other biologically active molecules contain sequences of at least three contiguous heteroatom-bearing carbons (triads). Important examples compounds that include such triads include Tamiflu® (oseltamivir phosphate) and Relenza® (zanamivir).
Molecules containing sequences of at least three contiguous heteroatom-bearing carbons are difficult to prepare, while synthetic methods for preparing two continuous heteroatom-bearing carbons are much further developed. Olefins are popular substrates for a host of oxidative transformations designed to introduce new C—N bonds into molecules. For example, the oxidative functionalization of olefins is a common method for the formation of vicinal carbon-heteroatom bonds. However, motifs having three contiguous heteroatom-bearing carbons can be difficult to prepare directly from simple hydrocarbon precursors, even reactive moieties such as olefins. Even more problematic is that the triads are difficult to prepare in enantioenriched form.
While much is known about the oxidative functionalization of olefins, considerably less is known about the oxidations of allenes, despite the potential to efficiently generate three new contiguous heteroatom-bearing chiral centers. New methods for the oxidation of allenes are therefore needed to add important flexibility to current synthetic methods. New methods for the preparation of synthetic motifs containing three contiguous carbon-heteroatom are also needed, for example, to provide more efficient syntheses of important biologically active molecules.
Additionally, chiral N,N-aminals are structural motifs found in many pharmaceuticals and biologically active natural products, such as the pyrroloindoline alkaloids, the phakellin-type pyrrole-imidazole alkaloids, and the lycoposerramines, many of which exhibit promising therapeutic activity. However, there are very few methods for the efficient preparation of chiral N,N-aminals. Thus, new methods are needed for the synthesis of N,N-aminals from readily available starting materials or intermediates.